The purpose of this research is to study the mechanisms of sensory transmission (chemical transmission) from chemoreceptor cells to afferent neurons in the carotid body. There are three objectives in the proposed project: the first two investigate whether putative neurotransmitter substances in the tissue (acetylcholine (ACh) and dopamine (DA) play a role in chemosensory transmission. In the ACh studies, we attempt to (1) localize the site of synthesis using autoradiography of the high affinity uptake of choline, and histochemistry of choline acetyltransferase activity, (2), study the effects of natural stimuli on the synthesis, turnover and release of 3H-ACh, and (3), determine the sites of binding of cholinergic ligands (125I-alpha-Bgt and 3H-QNB). In the DA studies, the experimental protocol parallels the ACh studies; i.e., localization of DA and the effects of natural stimuli on the synthesis, turnover and release of 3H-DA. Induction of tyrosine hydroxylase by natural stimuli is also examined. The principal effort will be to establish whether a close relationship exists between transmitter release and nerve activity, using for these experiments a specially-designed 'drop-chamber' for the simultaneous monitoring of carotid nerve impulse discharge and 3H-ACh and 3H-DA release. The third objective in the project is a study of chemotransduction and trophic relations within the glomus cell-nerve terminal complex. Experiments are planned using 2-deoxyglucose and 6-hydroxydopamine. Also the trophic dependency between the glomus cells and the sensory terminals will be studied. Methods include neurochemical (electrophoresis, radiometric and pyrolysis-GC/MS determinations), electrophysiological, and cyto-labelling techniques (autoradiography and histochemistry). It should be stressed that the carotid body is unique for such a combined neurochemical/electrophysiological study of sensory transmission because of its ease of isolation, the relatively large amount of receptor tissue at hand, and its viability for in vitro experimentation. Other 'secondary'-type receptors (i.e., receptors having specialized cells as pre-neural elements, such as the taste bud, Merkel's tactile receptor, and auditory hair cells, etc.) are less suitable because they lack one or more of these advantages.